Risk factors and treatment of relapses in autoimmune pancreatitis: Rituximab is safe and effective

Background and aims Steroid therapy is the first-line treatment for autoimmune pancreatitis but relapses are frequent. The aims were to assess the efficacy and the safety of immunomodulator treatments for relapsing autoimmune pancreatitis and rituximab in particular and to identify relapsing risk factors. Methods Patients followed for autoimmune pancreatitis from 2000 to 2016 were included. Data were retrospectively analysed regarding autoimmune pancreatitis treatment. Results In total, 162 patients with autoimmune pancreatitis type 1 (n = 92) and type 2 (n = 70) were included (median follow-up: 3 years (0.5–14). Relapse occurred in 46.5% of patients with autoimmune pancreatitis type 1 (vs 19.3% in autoimmune pancreatitis 2; p < 0.001). Risk factors of relapse were cholangitis, initial use of steroids, other organ involvement and chronic pancreatitis in autoimmune pancreatitis type 1 and initial use of steroids, tobacco consumption and chronic pancreatitis for autoimmune pancreatitis type 2. Overall, 21 patients were treated with immunomodulators (azathioprine, n = 19, or methotrexate, n = 2) for relapses. The efficiency rate was 67%. A total of 17 patients were treated with rituximab, with two perfusions at 15 days apart. The efficacy was 94% (16/17), significantly better than immunomodulator drugs (p = 0.03), with a median follow-up of 20 months (11–44). Only two patients needed two supplementary perfusions. Conclusion In relapsing autoimmune pancreatitis, rituximab is more efficient than immunomodulator drugs and shows better tolerance.

[1]  G. Capurso,et al.  Risk Factors for Rate of Relapse and Effects of Steroid Maintenance Therapy in Patients With Autoimmune Pancreatitis: Systematic Review and Meta‐analysis , 2019, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[2]  K. Dahan,et al.  Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients , 2017, PloS one.

[3]  S. Chari,et al.  Azathioprine Maintenance Therapy to Prevent Relapses in Autoimmune Pancreatitis , 2017, Clinical and Translational Gastroenterology.

[4]  S. Chari,et al.  International consensus for the treatment of autoimmune pancreatitis. , 2017, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.].

[5]  Jefte M. Drijvers,et al.  Clonal expansion of CD4(+) cytotoxic T lymphocytes in patients with IgG4-related disease. , 2016, The Journal of allergy and clinical immunology.

[6]  H. Sugimoto,et al.  Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis , 2016, Gut.

[7]  J. Stone,et al.  De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. , 2014, The Journal of allergy and clinical immunology.

[8]  K. Okazaki,et al.  Comprehensive Diagnostic Criteria for IgG4-Related Disease , 2014 .

[9]  I. Narita,et al.  The clinical course of patients with IgG4-related kidney disease. , 2013, Kidney international.

[10]  D. Furst,et al.  Long-term safety of rituximab in rheumatoid arthritis: 9.5-year follow-up of the global clinical trial programme with a focus on adverse events of interest in RA patients , 2012, Annals of the rheumatic diseases.

[11]  Wei-Chih Liao,et al.  Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis , 2012, Gut.

[12]  Michael J Levy,et al.  Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience , 2012, Gut.

[13]  T. Hibi,et al.  Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011 , 2012, Modern rheumatology.

[14]  J. Stone,et al.  Rituximab for the Treatment of IgG4-Related Disease: Lessons From 10 Consecutive Patients , 2012, Medicine.

[15]  Myung-Hwan Kim,et al.  International Consensus Diagnostic Criteria for Autoimmune Pancreatitis: Guidelines of the International Association of Pancreatology , 2011, Pancreas.

[16]  A. Sauvanet,et al.  Outcome of Patients With Type 1 or 2 Autoimmune Pancreatitis , 2011, The American Journal of Gastroenterology.

[17]  B. Petersen,et al.  Differences in clinical profile and relapse rate of type 1 versus type 2 autoimmune pancreatitis. , 2010, Gastroenterology.

[18]  T. Shimosegawa,et al.  Two clinicopathologic subtypes of autoimmune pancreatitis: LPSP and IDCP. , 2010, Gastroenterology.

[19]  F. Carrat,et al.  Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study , 2009, The Lancet.

[20]  M. Deheragoda,et al.  Presentation and management of post-treatment relapse in autoimmune pancreatitis/immunoglobulin G4-associated cholangitis. , 2009, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[21]  T. Shimosegawa,et al.  Standard steroid treatment for autoimmune pancreatitis , 2009, Gut.

[22]  B. Petersen,et al.  Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. , 2008, Gastroenterology.

[23]  N. Sasahira,et al.  Long-term prognosis of autoimmune pancreatitis with and without corticosteroid treatment , 2007, Gut.

[24]  H. Sarles,et al.  Chronic inflammatory sclerosis of the pancreas—An autonomous pancreatic disease? , 1961, The American Journal of Digestive Diseases.

[25]  G. Zamboni,et al.  Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens , 2004, Virchows Archiv.